Fusion proteins made up of glucagon-like peptide 1 (GLP-1) and exendin-4 (EX-4) fused to a nonglycosylated form of human transferrin (GLP-1-Tf or EX-4-Tf) were produced and characterized. GLP-1-Tf activated the GLP-1 receptor, was resistant to inactivation by peptidases, and had a half-life of approximately 2 days, compared with 1 to ...

Effects of intracerebroventricular (ICV) injection of calcitonin (CT) and calcitonin gene-related peptide (CGRP) on food and water intake were measured in two lines of White Plymouth Rock chickens from a common base population that have undergone long-term divergent selection for either low (LWS) or high (HWS) juvenile body weight. These ...

Many therapies designed to reduce food intake and body weight act, in part, by blocking the dopamine transporter (DAT) - a protein responsible for clearing extracellular dopamine (DA) after release thereby terminating its action. Here, we found that a single injection of the drug trodusquemine (MSI-1436) decreased food intake in ...

Exenatide is a synthetic agonist of the glucagon-like peptide-1 (GLP-1) receptor, which has also been shown to reduce food intake. The goal of this work is to test the hypothesis that exenatide reduces food intake and activates the enteric nervous system (ENS; myenteric and submucosal plexuses) of the gastrointestinal (GI) ...

Neuromedin S (NMS) is recognized as an anorexigenic peptide in the brain of mammals. In chicks (Gallus gallus), however, the effect of NMS has not been investigated. Therefore, the purpose of the present study was to investigate whether intracerebroventricular (ICV) injection of NMS affected feeding and drinking behavior in chicks. ...

When injected into adult or nymphal Locusta that have been deprived of food for 2h, immunogens such as laminarin and bacterial LPS can induce an almost immediate dose-dependent state of anorexia for at least 1h. Such anorexia is a component of a medley of physiological and behavioural changes called collectively ...

Nociceptin/orphanin FQ (N/OFQ), the nociceptin opioid peptide (NOP) receptor ligand, increases feeding when injected centrally. Initial data suggest that N/OFQ blocks the development of a conditioned taste aversion (CTA). The current project further characterized the involvement of N/OFQ in the regulation of hunger vs. aversive responses in rats by employing ...

It is well established that opioid signaling in the central nervous system constitutes a powerful stimulus for food intake. The role of opioids in determining food preference, however, is less well defined. Opioids have been proposed to promote intake of preferred foods, or, alternatively, to preferentially increase consumption of fat. ...

The central mechanism that mediates litorin-induced satiety is poorly understood, and has not been studied in a non-mammalian species. Therefore, the aim of this study was to determine if litorin-induced satiety in an alternative vertebrate model, the chick, and to elucidate some of the central mechanisms that are associated with ...

The hypothalamic melanocortin-4 receptor (MC4R) is a constituent of an important pathway regulating food intake and energy expenditure. We produced a monoclonal antibody (mAb) directed against the N-terminal domain of the MC4R and evaluated its potential as a possible therapeutic agent. This mAb (1E8a) showed specific binding to the MC4R ...

Brain-penetrable proline amides were developed as 5HT2c agonists with more than 1000-fold binding selectivity against 5HT2b receptor. After medicinal chemistry optimization and SAR studies, orally active proline amides with robust efficacy in a rodent food intake inhibition model were uncovered.

Melanocortin-3/4 receptor ligands administered to the caudal brain stem potently modulate food intake by changing meal size. The origin of the endogenous ligands is unclear, because the arcuate nucleus of the hypothalamus and the nucleus of the solitary tract (NTS) harbor populations of proopiomelanocortin (POMC)-expressing neurons. Here we demonstrate that ...

In submammalian vertebrates, corticotropin-releasing factor (CRF) acts as an anorexigenic neuropeptide as well as a potent stimulator of corticotropin and thyrotropin release from the pituitary. As a step for demonstrating the involvement of CRF in the feeding regulation of anuran larvae, which are known to stop feeding toward the metamorphic ...

Cannabis sativa (also known as marijuana) has been cultivated by man for more than 5,000 years. However, there was a rise in its use in the 20th century for recreational, religious or spiritual, and medicinal purposes. The main psychoactive constituent of cannabis, whose structure was identified in the 1960's, is ...

Opioid signaling has been strongly implicated in driving palatable food consumption. The nucleus accumbens (NAcc) is one important site of this effect; hyperphagia elicited by administration of exogenous mu opioid receptor (MOR) ligands in this brain region has been well documented. However, the role that endogenous opioid ligands in the ...

It is unclear what contribution food intake and metabolism have in causing weight loss after administering a dose of nicotine equivalent to smoking one to three packs of cigarettes per day because previous studies have been of a very short duration. To address this question, male Sprague Dawley rats were ...

In view of its potential advantages, drug polytherapy is currently attracting significant interest in the field of obesity research. In this context, concurrent manipulation of serotonergic and cannabinoid pathways in rodents has been found to reduce food and fluid intake in both an additive or synergistic manner. To further assess ...

Nesfatin-1 is recently reported as a satiety molecule to suppress food intake via the melanocortin signaling in hypothalamus when injected centrally and peripherally. Here we report that nesfatin-1 is also anti-hyperglycemic. It was found that the intravenous injection of nesfatin-1 significantly reduced blood glucose in hyperglycemic db/db mice. This anti-hyperglycemic ...

The cachexia-anorexia syndrome, in which patients suffering from chronic illness lack the desire to eat and experience weight loss, creates a serious clinical problem when patients are attempting to overcome the disease process. Endotoxin (ET) has many actions in the brain and peripheral injections can affect regulation of monoamines in ...

BACKGROUND: Specialized hypothalamic systems that increase food intake might also increase ethanol intake. To test this possibility, morphine and receptor-specific opioid agonists were microinjected in the paraventricular nucleus (PVN) of rats that had learned to drink ethanol. To cross-validate the results, naloxone methiodide (m-naloxone), an opioid antagonist, was microinjected with ...

The effects of the protein synthesis inhibitor cycloheximide and serotonin and NMDA glutamate receptor antagonists on the processes of consolidation of an associative skill consisting of refusing a particular foodstuff were studied in the common snail. When animals were trained on the background of cycloheximide, the skill was not acquired. ...

Sibutramine is one of a small number of clinically approved anti-obesity agents while naloxone not only has intrinsic anorectic efficacy but, in low doses, also produces additive/synergistic anorectic effects in combination with other compounds. In view of the potential advantages of drug polytherapy over conventional monotherapy, the present study explored ...

It has been suggested that the activation of cannabinoid receptors in the nucleus accumbens shell facilitates feeding behavior. However, it remains unclear whether cannabinoid ligands enhance the palatability of food to facilitate feeding. In this study, we examined whether microinjecting an endogenous cannabinoid agonist, anandamide into the nucleus accumbens shell ...

Neuropeptide S (NPS) is a recently discovered neurotransmitter that binds to its cognate G-protein coupled receptor, NPSR. Previous studies have shown that central administration of this peptide induces anxiolytic-like effects, promotes arousal and inhibits feeding in the same dose range. In the present study, we sought to investigate further the ...

Substantial evidence suggests that pharmacological manipulations of neural serotonin pathways influence ingestive behaviors. Despite the known role of the nucleus accumbens in directing appetitive and consummatory behavior, there has been little examination of the influences that serotonin receptors may play in modulating feeding within nucleus accumbens circuitry. In these experiments, ...

RATIONALE: Compounds which decrease NMDA receptor functioning, such as PCP and ketamine have abuse liability, whereas co-agonists of the NMDA receptor attenuate some of the behavioral and neurochemical effects of stimulant drugs. Here we examined the effects of a glycine transporter (GlyT1) inhibitor, which elevates glycine and hence NMDA signaling, ...

Male Sprague-Dawley rats were fitted with two cannulae in the VTA and one cannula in the NTS for co-administration of the micro-opioid receptor agonist DAMGO in one site and the opioid antagonist naltrexone in the other. Injection of DAMGO into the VTA or the NTS stimulated feeding. The increase in ...

Glucagon-like peptide (GLP)-1 is a regulatory peptide synthesized in the gut and the brain that plays an important role in the regulation of food intake. Both GLP-1 and exendin (Ex)-4, a long-acting GLP-1 receptor (GLP-1r) agonist, reduce food intake when administered intracerebroventricularly, whereas Ex4 is much more potent at suppressing ...

A series of pyrimidine analogues derived from ATC0175 were potent antagonists of human MCH-R1 in vitro. Significantly improved receptor selectivity was achieved with several analogues from this series, but no improvement in brain partitioning was noted. One example from this series was shown to inhibit food intake and decrease body ...

We found that beta-lactotensin (His-Ile-Arg-Leu), which has been isolated as an ileum-contracting peptide from chymotrypsin digest of bovine beta-lactoglobulin, dose-dependently suppresses food intake after intracerebroventricular (i.c.v.) or intraperitoneal administration at a dose of 40 nmol/mouse or 100mg/kg, respectively, in fasted mice. Orally administered beta-lactotensin also suppressed food intake at 500 ...

The role of gamma melanocyte stimulating hormone (gamma-MSH) in appetite regulation is controversial in mammals and to our knowledge unreported within the avian class. Thus, the present study was designed to determine the effects of intracerebroventricularly (i.c.v.) administered gamma2-MSH on food intake using Cobb-500 chicks as models. In Experiment 1, ...

The nucleus accumbens (NAc) participates in the control of both motivation and addiction. To test the possibility that opioids in the NAc can cause rats to select ethanol in preference to food, Sprague-Dawley rats with ethanol, food, and water available, were injected with two doses each of morphine, the mu-receptor ...

Oxyntomodulin (OXM) is a peptide released from the gut and attenuates food intake by acting on hypothalamus. However, its role at the molecular level is not well studied. In the first section of this study, we analysed the effect of OXM on food intake behaviour after injecting into the lateral ...

The present experiments were conducted to provide a more detailed behavioral analysis of the dissociable roles of the basolateral (BLA) and central nucleus (CeA) of the amygdala in mediating intra-accumbens (Acb) opioid-induced feeding of a high-fat diet. Confirming previous findings, temporary inactivation of the CeA with the GABAA agonist muscimol ...

Although LPLRFamide was the first member of the RFamide family to be isolated from a vertebrate species, its effects on hunger and satiety-related processes are poorly documented. Thus, we intracerebroventricularly administered LPLRFamide (3.0-15.0 nmol) to both Cobb-500 (a broiler type of Gallus gallus) and Bobwhite quail (Colinus virginianus) chicks and ...

RATIONALE: Drugs that interfere with cannabinoid CB1 transmission suppress food-motivated behaviors and may be useful as appetite suppressants, but there is uncertainty about the locus of action for the feeding-suppression effects of these drugs. OBJECTIVE: The present work was conducted to determine if two drugs that interfere with cannabinoid receptor ...

The neurotensin-1 (NT1) receptor has been implicated in mediating a number of important neurotensin effects. We have found that PD149163, a selective, brain-penetrating, NT1 receptor agonist, produces a number of therapeutic-like preclinical effects after peripheral administration including pro-cognitive, antipsychotic and anxiolytic effects. In this study, we investigated PD149163's effect on ...

Menopause is one of the triggers that induce obesity. Estradiol (E2), corticotropin-releasing hormone (CRH), and hypothalamic neuronal histamine are anorexigenic substances within the hypothalamus. This study examined the interactions among E2, CRH, and histamine during the regulation of feeding behavior and obesity in rodents. Food intake was measured in rats ...

RATIONALE: The cannabinoid CB1 selective antagonist SR141716A (Rimonabant) has been shown to decrease body weight in laboratory animals and humans. Furthermore, SR141716A can elicit scratching behavior in rodents, a behavior that has been hypothesized to contribute to SR141716A-induced decrease in food intake. Although childhood obesity is a rising health issue, ...

Neuropeptide AF (NPAF), a member of the RFamide family, is encoded by the same gene as neuropeptide FF (NPFF), which causes short-term anorexia. However, reports on the role of NPAF on appetite-related process are lacking. Thus, i.c.v. injections of 4.0, 8.0 and 16.0 nmol NPAF were administered to chicks to ...

To our knowledge appetite-associated effects of neuropeptide SF (NPSF) are unreported. Thus chicks were intracerebroventricularly injected with 3.8, 7.5 and 15.0 nmol of NPSF and they reduced both their food and water intake. Blood glucose concentration was not affected. Additionally, NPSF-treated chicks did not exhibit any behaviors that were associated ...

The lateral hypothalamus (LH) is a site of integration for control mechanisms of feeding behavior as it has extensive reciprocal connections with multiple intrahypothalamic and extrahypothalamic brain areas. Evidence suggests that blockade of ionotropric gamma-aminobutyric acid (GABA) receptors in the LH elicits eating in satiated rats. To determine whether this ...

A series of 2-pyridone-containing imidazoline derivatives was synthesized and evaluated as neuropeptide Y Y5 receptor antagonists. Optimization of the 2-pyridone structure on the 2-position of the imidazoline ring led to identification of 1-(difluoromethyl)-5-[(4S,5S)-4-(4-fluorophenyl)-4-(6-fluoropyridin-3-yl)-5-methyl-4,5-dihydro-1H-imidazol-2-yl]pyridin-2(1H)-one (7m). Compound 7m displayed statistically significant inhibition of food intake in an agonist-induced food intake model in ...